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Diabetes Management DPP-4 Inhibitors
digitoxin—medications often taken by patients with type 2 diabetes.
20–23
A
small pilot study investigating the pharmacokinetics of saxagliptin in Baptist Gallwitz, MD, PhD, is a Professor of Medicine in the
patients with hepatic dysfunction shows a slower metabolization of
Department of Medicine IV at Eberhard Karls University of
Tübingen, where his clinical position is Head of the
saxaglitpin, but no severe side effects.
31
A study on patients with renal
Outpatient Department for Endocrinology and Diabetes. He
impairment is under way.
17
is a member of the American Diabetes Association (ADA),
the European Association for the Study of Diabetes
(EASD), the German Diabetes Association, and various other
In a head-to-head study, saxagliptin was non-inferior to sitagliptin.
33
A
scientific and medical associations. He is also a member of
meta-analysis of the existing phase II and III studies showed favorable various Editorial Boards of international diabetes journals.
cardiovascular outcomes in the saxagliptin-treated patients (see
Professor Gallwitz’s main scientific focus is the physiology of incretin hormones. He was
Figure
Senior Registrar from 1999 and held a teaching post (Associate Professor) at the St Josef-
5).
34
The development of saxagliptin and the other DPP-4 inhibitors
Hospital Medical School, Ruhr-University Bochum until 2003, when he joined Tübingen
emphasizes the advantages of DPP-4 inhibitors over classic insulin University. He specialized in internal medicine, endocrinology, and gastroenterology at the
secretagogs (sulfonylureas and metiglinides) regarding their glucose-
Universities of Göttingen and Kiel. After university and medical school in Essen, Berlin,
London, and Munich, he finished his doctoral thesis on insulin signal transduction at the
dependent action without intrinsic risk of hypoglycemia and their
Diabetes Research Institute, University of Munich in 1986.
weight neutrality.
35
n
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2. Prentki M, Nolan CJ, Islet beta cell failure in type 2 diabetes, potent dipeptidyl peptidase IV inhibitors, Bioorg Med Chem Lett, 27. Chacra AR, Tan GH, Apanovitch A, et al., Saxagliptin added to
J Clin Invest, 2006;116:1802–12. 2005;15:3992–5. a submaximal dose of sulphonylurea improves glycaemic
3. Gallwitz B, Therapies for the treatment of type 2 diabetes 16. Augeri DJ, Robl JA, Betebenner DA, et al., Discovery and control compared with uptitration of sulphonylurea in
mellitus based on incretin action, Minerva Endocrinol, preclinical profile of Saxagliptin (BMS-477118): a highly patients with type 2 diabetes: a randomised controlled trial,
2006;31:133–47. potent, long-acting, orally active dipeptidyl peptidase IV Int J Clin Pract, 2009;63:1395–1406.
4. Creutzfeldt W, The incretin concept today, Diabetologia, inhibitor for the treatment of type 2 diabetes, J Med Chem, 28. Jadzinsky M, Pfützner A, Paz-Pacheco E, et al., Saxagliptin
1979;16:75–85. 2005;48:5025–37. given in combination with metformin as initial therapy
5. Nauck MA, Heimesaat MM, Orskov C, et al., Preserved incretin 17. Gallwitz B, Saxagliptin, a dipeptidyl peptidase IV inhibitor for improves glycaemic control in patients with type 2 diabetes
activity of glucagon-like peptide 1 [7-36 amide] but not of the treatment of type 2 diabetes, IDrugs, 2008;11:906–17. compared with either monotherapy: a randomized
synthetic human gastric inhibitory polypeptide in patients with 18. Deacon CF, Holst JJ, Saxagliptin: a new dipeptidyl peptidase- controlled trial, Diabetes Obes Metab, 2009;11:611–22.
type-2 diabetes mellitus, J Clin Invest, 1993;91:301–7. 4 inhibitor for the treatment of type 2 diabetes, Adv Ther, 29. DeFronzo RA, Hissa MN, Garber AJ, et al., The efficacy and
6. Drucker DJ, Nauck MA, The incretin system: glucagon-like 2009;26:488–99. safety of saxagliptin when added to metformin therapy in
peptide-1 receptor agonists and dipeptidyl peptidase-4 19. Fura A, Khanna A, Vyas V, et al., Pharmacokinetics of the patients with inadequately controlled type 2 diabetes with
inhibitors in type 2 diabetes, Lancet, 2006;368:1696–1705. dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and metformin alone, Diabetes Care, 2009;32:1649–55.
7. Zander M, Madsbad S, Madsen JL, et al., Effect of 6-week monkeys and clinical projections, Drug Metab Dispos, 30. Rosenstock J, Sankoh S, List JF, Glucose-lowering activity of
course of glucagon-like peptide 1 on glycaemic control, 2009;37:1164–71. the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive
insulin sensitivity, and beta-cell function in type 2 diabetes: a 20. Girgis S, Patel CG, Li L, et al., Effect of diltiazem on the patients with type 2 diabetes, Diabetes Obes Metab, 2008;10:
parallel-group study, Lancet, 2002;359:824–30. pharmacokinetics of saxagliptin in healthy subjects. J Clin 376–86.
8. Drucker DJ, The biology of incretin hormones, Cell Metab, Pharmacol [36th Annu Meet Am Coll Clin harmacol (ACCP) (Sept 9-11, 31. Patel C, Castaneda L, Frevert U, et al., Single-dose
2006;3:153–65. San Francisco) 2007] 2007;47(9): abstract 72.  pharmacokinetics and safety of saxagliptin in subjects with
9. Mentlein R, Dipeptidyl-peptidase IV (CD26)—role in the 21. Boulton DW, Brenner E, Royzman K, et al., Effect of hepatic impairment compared with healthy subjects,
inactivation of regulatory peptides, Regul Pept, 1999;85:9–24. ketoconazole on the pharmacokinetics of saxgaliptin in Diabetes Care, 2008;57(Suppl. 1):537 P.
10. Karasik A, Aschner P, Katzeff H, et al., Sitagliptin, a DPP-4 healthy subjects, J Clin Pharmacol, 2007;47:1203. 32. Ahren B, Schweizer A, Dejager S, et al., Vildagliptin enhances
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of type 2 diabetes, Expert Opin Investig Drugs, 2008;17:105–13. S92–S93. October 5, 2009.
12. Thornberry NA, Gallwitz B, Mechanism of action of inhibitors 23. Boulton DW, Li L, Patel CG, et al., No pharmacokinetic 34. Wolf R, Frederich R, Fiedorek F, et al., Evaluation of CV risk in
of dipeptidyl-peptidase-4 (DPP-4), Best Pract Res Clin Endocrinol interaction between saxagliptin and digoxin in healthy the saxagliptin clinical trials, Diabetes, 2009;59(Suppl. 1):8-LB.
Metab, 2009;23:479–86. subjects, Clin Pharmacol Ther, 2008;83(Suppl. 1):S93. 35. Gallwitz B, Häing HU, Future perspectives for insulinotropic
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593–607. Ther, 2009;26:736. of print).
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74 US ENDOCRINOLOGY
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